1.3- Dioxane, 2- bromomethyl -2-

Chlorination of 5-hydroxyquinoxaline 1,4-dioxide in methylene chloride gives the 6,8-dichloro derivative, but reaction with N-chlorosuccinimide yields 8-chloro-5-hydroxyquinoxaline dioxide. Bromination in acetic acid gives the 6,8-dibromo derivative.195 15 Side-chain bromination is observed, however, when 2,3-dimethylquinoxaline 1,4-dioxide reacts with bromine in dioxane 2,3-bis(bromomethyl)quin-oxaline 1,4-dioxide is formed.195c... 

A. 2-( Bromomethyl)- .-( ehloromethyD-1, -dioxane. A 100-mL, round-bottomed flask is equipped with a 10-mL Dean-Stark apparatus and a condenser. The flask is charged with 30.0 g (0.138 mol) of l-bromo-3-chloro-2,2-dimethoxypropane (Note 1), 10.0 mL (0.138 mol) of 1,3-propanediol (Note 2), and 3 drops of concentrated sulfuric acid. The resulting solution is heated (bath temperature 140°C) for 8 hr (Note 3) with distillative removal of methanol (ca. 11 mL). The mixture is allowed to cool to room temperature and the crude product is partitioned in 150 mL of pentane and 40 mL of water. The... 

Trimethyl-l,3-dioxane-2-yl)thiophene 2-Bromoethyl methylether 2-(Bromomethyl)ethyl methyl ether Propylamine... 

Methyl-1,5-naphthyridine 1,5-dioxide (42, R=H) gave 2-bromomethyl-l, 5-naphthyridine 1,5-dioxide (42, R=Br) (dioxane dibromide 81% for further details, see original).290 See also Section 3.1.1. 

The application of the Wurtz coupling for the synthesis of [2.2](2,6)pyridinophane (85) from 2,6-bis(bromomethyl)pyridine (86) was already attempted in the fifties by Baker et al. [68]. Yet, the desired cyclophane could not be found. However, the intramolecular cyclization of 87 with phenyl Uthium or butyl lithium in ether led to in 3 and 28% yield, respectively [68]. The iwteraiolecular cyclization of 86 with phenyl lithium in dioxane gives a 9% yield of 85, too [69]. 

Bromination of 23-diniethylpyrazine 1,4-dioxide in dioxane in the presence of benzoyl peroxide gave 2-(bromomethyl)-3-methyl- and 2,3-bis(bromomethyl)-pyrazine 1,4-dioxide (739), and 2-methylpyrazine 1,4-dioxide gave 2-bromo-... 

Benzyl-3 -bromomethyl-5-chloro-6-phenyl-2( l//)-pyrazin( )nc (240) gave l-benzyl-5-chloro-3-hydroxymethyl-6-phenyl-2(lF/)-pyrazinone (241) (K2CO3, H2O—dioxane, reflux, 2 h 68% note survival of the chloro substituent). ... 

Several new azepinium salt catalysts, derived from (- -)- and (—)-5-amino-2,2-dimethyl-4-phenyl-l,3-dioxane 23 [39] and (—)-isopinocamphenylamine 17 moieties, and fused to R or S binaphthalene units [40,41], were directly prepared, in good yields, from the bromomethyl carbaldehyde intermediate 32, which we prepared in turn from commercial R or S (l,l )-binaphthalenyl-2,2 -diol (Binol) (Scheme 5.20, Table 5.4). 

The presence of a reverse anomeric effect was suggested (29) for chlo-romethyl, CICH2—, and bromomethyl, BrCHj—, groups located at the anomeric carbon atom of a 1,3-dioxane ring. This claim was based on the observed reversed dependence of axial preference on solvent polarity, that is, more polar solvents increased the population of axial conformers. This observation is in line with the fact that a-glucopyranosylimidazoles in water (very polar solvent) do not change conformation on protonation (162). 

Condensation reactions offer a convenient route to the benzo-l-thia-2,4-diazine 1,1-dioxide system. Thus, exposure of sulfonamide 179 to acid in boiling 1,4-dioxane results in formation of the 3-(bromomethyl) derivative 180 (Equation 32) <2005BML1185>. The analogous compound 181 is cyclized readily in the presence of base to afford the 2//-benzo-l-thia-2,4-diazine 1,1-dioxide 135 in 71% yield (Equation 33) <2001JME3488>. Reaction of the carboethoxy group of 135 with amines is discussed in Section 9.05.7.5. 

A mixture of 1.5 g 5-bromomethyl-3,3-dimethyl-2-phenyltetrahydro-2-furanol ( bromo-hydrin ), 2.5 mL 10% NaOH, and 50 mL dioxane was stirred and refluxed for 4 h and then poured into 1 L water. The mixture was extracted with four 200-mL portions of ether. The organic layers were combined and washed with 100 mL water (hve times) and 40 mL brine (three times). Removal of the ether at room temperature left 1.22 g orange oil, which was chromatogrphed from petroleum ether on 37.0 g alumina. Elution with petroleum ether and 10 1 petroleum ether/ether gave 0.75 g of a white solid (the starting material) and 0.36 g 2-hydroxy-5-hydroxymethyl-3,3-dimethyl-2-phenyltetrahydrofuran as a white solid, in a yield of 30%. 

A soln. of methyl 3-bromo-2-bromomethyl-4-hydroxy-6-methoxybenzoate in dioxane-water refluxed 44 hrs. 4-bromo-5-hydroxy-7-methoxyphthalide. Y 1. E. M. Howells and G. T. Newbold, Soc. 1965, 4592. 

One vital observation made by Nierenstein was that there was a considerable reluctance of acyl bromides to form the corresponding bromomethyl ketones. Acid bromides on reaction with diazomethane were also found to form substituted 1,4-dioxanes or specifically 3,6-dibromo-3,6-diphenyl-1,4-dioxane 8, resulting from the dimerization of adducts. The dimerization according to him could be attributed to the poor mobility of the bromide compared to the chloride group. 

The coupling reaction between 2,ll-diaza[3.3]metacyclophane and 1,3-bis(bromomethyl)benzene in the presence of NaH in dioxane or toluene gave the dimer and the trimer in Fig. 1. 

A soln. of Ag-nitrate in dioxane-water added to a soln. of 5-bromomethyl-llH-benzo[a]fluoren-ll-one in dioxane, and stored 2 hrs. at room temp. 5-nitrato-methyl-llH-benzo[a]fluoren-ll-one (Y 94%) refluxed 2 hrs. with KOH in dioxane-water llH-benzo[a]fluoren-ll-one-5-carboxaldehyde (Y 91.5%). R. L. Letsinger and J. D. Jamison, Am. Soc. 93, 193 (1961). 

N-Bromosuccinimide and 70%-perchloric acid added to a soln. of 10 g. 16-methylene-17a-hydroxyprogesterone in dioxane-water, and allowed to stand 1 hr. at room temp. 10.8 g. 16j -bromomethyl-16a,17a-oxidoprogesterone refluxed 1 hr. with ca. 6 g. HBr in ether-dioxane 16-bromomethylene-17a-hydroxyprogesterone (Y 79%). F. e. with other halogens s. F. v. Werder et al., B. 95, 2110 (1962). 

Then, 28 g (0.115 mol) of bis(bromomethyl)oxacyclobutane dissolved in a mixed solvent of 94 ml of methanol and 28 ml of water was added dropwise into a solution of 44.8 g (0.358 mol) of Na2S03 dissolved in 252 ml of water. The resulting mixture was refluxed for about 3.5 h, and the solvent was removed under vacuum. The residue was treated with 200 ml of concentrated HCl, and filtered to remove NaCl, thereby obtaining a sulfonic acid solution, which was then evaporated in a vacuum. The resulting residue oil was heated at about 2 ton at about 210-220°C for about 2hto obtain a black mass, which was then extracted with boiling dioxane and then filtered in the hot state. The filtrate was cooled down to crystallize 10 g of disultone. 

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